Project Summary/Abstract Eradication of bacteria located in periodontal pockets presents a daunting challenge to dentists and oral care professionals. The problem is significant; severe periodontitis is the 6th most prevalent disease worldwide with over 743 million people affected. The global cost of lost productivity from severe periodontitis is estimated to be $54 billion USD/year. Antibiotics with scaling and root planing (SRP) have been the mainstays of current treatments but may lead to the development of antibiotic- resistant bacteria. Photodynamic therapy (PDT) is a beneficial alternative, however, there are several challenges to its implantation including staining of tissue and a short penetration depth because the dye is introduced directly into the periodontal pocket as well as long treatment times due lack of oxygen in hypoxic pockets. Thus, there is an urgent need for further advances in periodontal bacteria eradication. The superhydrophobic fiber optic PDT (SH-PDT) device tip developed by SingletO2 Therapeutics LLC delivers bactericidal singlet oxygen (1O2, a cytotoxic excited state of molecular oxygen) in a direct, controllable fashion. This device is a major breakthrough for the precise delivery of reactive singlet oxygen to kill hypoxic bacteria for treatment of periodontal diseases. Using precision molding and 3D printing technologies, the device integrates a sensitizer onto the tip of an optical fiber that can painlessly be inserted between the tooth and gum killing bacteria which are the cause of periodontitis. Our superhydrophobic design prevents contact between biofluids and the sensitizer, eliminating staining. Moreover, disinfection of the periodontal pocket will be achieved in a single visit due to the efficiency of the superhydrophobic system to trap air, which will provide oxygen to otherwise hypoxic environments. The approach will also not induce bacterial resistance, and it will be equally effective on gram-negative and gram-positive bacteria. In this Phase II STTR project, we propose to study the efficacy of the SH-PDT device in two ways. First we will quantify the ability of the device to kill a bacterial biofilm in vitro that is comprised of three different bacteria strains associated with periodontitis. Secondly, we will quantify the ability of the device to kill periodontitis in vivo using a Wistar rat ligature model. A pilot study will be conducted to determine the appropriate dose, followed by a full study to acquire statistically significant results. Successful results from these studies will be used to design human clinical trials in the future.